A reproducible experimental animal model is necessary for the elucidation of the pathogenetic mechanism and a rational antiviral treatment of recurrent oro-facial herpes simplex virus (HSV) infections. An important question of my research project is whether, during recurrences, the information for virus synthesis persists at the site of the latent infection, or whether the entire information is channeled to the site of recurrences and latency is maintained through successive reinfections of the ganglia. The first objective of the project is the development of an experimental model of recurrent herpes in mice and guinea pigs in which spontaneous and induced recurrences can be obtained. Inducing agents acting on the skin and on the immune system will be tested. The effect of antiviral treatments upon the frequency of recurrences and the persistence of latent infections in the ganglia will be studied. The possible emergence of drug-resistant HSV, rescued from latently infected ganglia, after antiviral treatment, will be investigated. The second objective is the study of humoral and cell-mediated immune responses after antiviral treatment and during recurrences. The relative protection of interferon-treated cells against HSV challenge, as well as the role played by interferon in the resistance to reinfection in HSV-infected survivors, constitutes the last area of the proposed investigations.